β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest
ObjectiveColorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation...
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.00378/full |
| _version_ | 1818991032853856256 |
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| author | Ruonan Zhang Ruonan Zhang Ruonan Zhang Ting Pan Ting Pan Yu Xiang Yu Xiang Mingming Zhang Mingming Zhang Jiao Feng Jiao Feng Shuiping Liu Shuiping Liu Ting Duan Ting Duan Peng Chen Peng Chen Bingtao Zhai Bingtao Zhai Xiaying Chen Xiaying Chen Wengang Wang Wengang Wang Bi Chen Bi Chen Bi Chen Xuemeng Han Xuemeng Han Liuxi Chen Liuxi Chen Lili Yan Lili Yan Ting Jin Ting Jin Ying Liu Guohua Li Guohua Li Xingxing Huang Xingxing Huang Wenzheng Zhang Wenzheng Zhang Yitian Sun Yitian Sun Qiujie Li Qiujie Li Qin Zhang Qin Zhang Lvjia Zhuo Lvjia Zhuo Tian Xie Tian Xie Qibiao Wu Xinbing Sui Xinbing Sui Xinbing Sui |
| author_facet | Ruonan Zhang Ruonan Zhang Ruonan Zhang Ting Pan Ting Pan Yu Xiang Yu Xiang Mingming Zhang Mingming Zhang Jiao Feng Jiao Feng Shuiping Liu Shuiping Liu Ting Duan Ting Duan Peng Chen Peng Chen Bingtao Zhai Bingtao Zhai Xiaying Chen Xiaying Chen Wengang Wang Wengang Wang Bi Chen Bi Chen Bi Chen Xuemeng Han Xuemeng Han Liuxi Chen Liuxi Chen Lili Yan Lili Yan Ting Jin Ting Jin Ying Liu Guohua Li Guohua Li Xingxing Huang Xingxing Huang Wenzheng Zhang Wenzheng Zhang Yitian Sun Yitian Sun Qiujie Li Qiujie Li Qin Zhang Qin Zhang Lvjia Zhuo Lvjia Zhuo Tian Xie Tian Xie Qibiao Wu Xinbing Sui Xinbing Sui Xinbing Sui |
| author_sort | Ruonan Zhang |
| collection | DOAJ |
| description | ObjectiveColorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of β-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53–/–, and determine the possible molecular mechanism of β-elemene to reverse 5-fluorouracil resistance.MethodsThe effect of β-elemene on HCT116p53–/– cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in β-elemene reversing the resistance of HCT116p53–/– to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of β-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53–/– all line xenograft model.ResultsFor p53 wildtype colorectal cancer cells, β-elemene could augment the sensitivity of 5-fluorouracil, for p53-deficient colorectal cancer cells, β-elemene significantly inhibited cell proliferation in a concentration-dependent manner, and reversed the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest.Conclusionβ-elemene enhances the sensitivity of p53 wild-type cells to 5-fluorouracil, β-elemene can reverse the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest in p53-deficient colorectal cancer, which will provide a new method for the treatment of p53 deletion colorectal cancer patients. |
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| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-20T20:03:49Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-106f9dd1307d465cb08047cea667f0932022-12-21T19:27:59ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-05-01810.3389/fbioe.2020.00378542233β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle ArrestRuonan Zhang0Ruonan Zhang1Ruonan Zhang2Ting Pan3Ting Pan4Yu Xiang5Yu Xiang6Mingming Zhang7Mingming Zhang8Jiao Feng9Jiao Feng10Shuiping Liu11Shuiping Liu12Ting Duan13Ting Duan14Peng Chen15Peng Chen16Bingtao Zhai17Bingtao Zhai18Xiaying Chen19Xiaying Chen20Wengang Wang21Wengang Wang22Bi Chen23Bi Chen24Bi Chen25Xuemeng Han26Xuemeng Han27Liuxi Chen28Liuxi Chen29Lili Yan30Lili Yan31Ting Jin32Ting Jin33Ying Liu34Guohua Li35Guohua Li36Xingxing Huang37Xingxing Huang38Wenzheng Zhang39Wenzheng Zhang40Yitian Sun41Yitian Sun42Qiujie Li43Qiujie Li44Qin Zhang45Qin Zhang46Lvjia Zhuo47Lvjia Zhuo48Tian Xie49Tian Xie50Qibiao Wu51Xinbing Sui52Xinbing Sui53Xinbing Sui54Department of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDepartment of Medical Oncology, Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, ChinaObjectiveColorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of β-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53–/–, and determine the possible molecular mechanism of β-elemene to reverse 5-fluorouracil resistance.MethodsThe effect of β-elemene on HCT116p53–/– cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in β-elemene reversing the resistance of HCT116p53–/– to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of β-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53–/– all line xenograft model.ResultsFor p53 wildtype colorectal cancer cells, β-elemene could augment the sensitivity of 5-fluorouracil, for p53-deficient colorectal cancer cells, β-elemene significantly inhibited cell proliferation in a concentration-dependent manner, and reversed the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest.Conclusionβ-elemene enhances the sensitivity of p53 wild-type cells to 5-fluorouracil, β-elemene can reverse the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest in p53-deficient colorectal cancer, which will provide a new method for the treatment of p53 deletion colorectal cancer patients.https://www.frontiersin.org/article/10.3389/fbioe.2020.00378/fullcolorectal cancerp53β-elemene5-fluorouracilautophagycell cycle |
| spellingShingle | Ruonan Zhang Ruonan Zhang Ruonan Zhang Ting Pan Ting Pan Yu Xiang Yu Xiang Mingming Zhang Mingming Zhang Jiao Feng Jiao Feng Shuiping Liu Shuiping Liu Ting Duan Ting Duan Peng Chen Peng Chen Bingtao Zhai Bingtao Zhai Xiaying Chen Xiaying Chen Wengang Wang Wengang Wang Bi Chen Bi Chen Bi Chen Xuemeng Han Xuemeng Han Liuxi Chen Liuxi Chen Lili Yan Lili Yan Ting Jin Ting Jin Ying Liu Guohua Li Guohua Li Xingxing Huang Xingxing Huang Wenzheng Zhang Wenzheng Zhang Yitian Sun Yitian Sun Qiujie Li Qiujie Li Qin Zhang Qin Zhang Lvjia Zhuo Lvjia Zhuo Tian Xie Tian Xie Qibiao Wu Xinbing Sui Xinbing Sui Xinbing Sui β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest Frontiers in Bioengineering and Biotechnology colorectal cancer p53 β-elemene 5-fluorouracil autophagy cell cycle |
| title | β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest |
| title_full | β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest |
| title_fullStr | β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest |
| title_full_unstemmed | β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest |
| title_short | β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest |
| title_sort | β elemene reverses the resistance of p53 deficient colorectal cancer cells to 5 fluorouracil by inducing pro death autophagy and cyclin d3 dependent cycle arrest |
| topic | colorectal cancer p53 β-elemene 5-fluorouracil autophagy cell cycle |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2020.00378/full |
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